Title: Antihyperglycemic, antihyperlipidemic and antioxidant activity of phenolic rich extract of Brassica oleracea var gongylodes on streptozotocin induced Wistar rats
Authors: Indumati Sharma, Mallikarjun Aaradhya, Madhuri Kodikonda and Prakash Ramchandra Naik
Published: March 26, 2015
Read or Download the PDF: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439412/pdf/40064_2015_Article_948.pdf
Cruciferous vegetables, in particular those included into the Brassica genus, are good sources of a variety of nutrients and health-promoting phytochemicals. Phenolic compounds are the major antioxidants of Brassica; hence the contribution of Brassica vegetables to health improvement has largely been associated to their antioxidant capacity. This study aimed to assess anti-diabetic, antilipidemic, and antioxidant activity of phenolic rich extract of Brassica oleracea var gongylodes (BOvG) in Wistar rats. The findings revealed that the administration of BOvG extract to diabetic rats significantly reduced fasting blood glucose by 64% within 7 days of treatment. Additionally, BOvG extract was also observed to normalize the diabetic rats’ lipid profile and HbA1c (Glycated hemoglobin). BOvG extract also showed protection of liver- kidney functions, which was evidenced by the significant decrease in Blood Urea Nitrogen (BUN), Serum glutamic oxaloacetic transaminase (SGOT) and Serum glutamic pyruvic transaminase (SGPT). The treatment also improved the antioxidant status of the diabetic rats where the enzymatic activities of Catalase (CAT) and Super Oxide Dismutase (SOD) were significantly increased. Furthermore, RP-HPLC analysis detected chlorogenic acid, rutin, and sinapic acid against known standards in BOvG extract. Hence, the present investigation suggests that BOvG phenolic rich extract (as a multi-component therapy) exhibited anti-diabetic, antilipidemic and antioxidant properties in STZ-induced diabetic rats.
In the last few decades, there has been a tremendous increase in the prevalence of type 2 diabetes internationally, and has been estimated that the number of diabetic patients will be more than 205 million in the next 20 years (Diabetes Atlas and 6th Edition 2014). Oral hypoglycemic agents and insulin, generally used to treat Diabetes Mellitus (DM), have number of serious side effects (Kyriacou and Ahmed 2010). Hence, interest has increased in finding naturally occurring anti-diabetic therapeutics to replace synthetic drugs (Velioglu et al. 1998). As there have been increasing emphasis on the promotion of a healthy diet for the management of type 2 diabetes, there is a great necessity to investigate the combination of drugs derived from natural resource extracts (Kaur et al. 2013).
Numerous studies have established an inverse correlation between the intake of fruits and vegetables and the onset of diseases such as diabetes, cardiovascular disease, cancer, and aging-related disorders as they are rich source of dietary antioxidants, including polyphenolics, vitamins E and C, and carotenoids (Huang et al. 2005). Polyphenolic compounds, in particular, have been shown to terminate free radical chain reactions in biological systems, and hence can act as nutraceuticals for a range of oxidative stress implicated diseases, like diabetes and cancer (Espín et al. 2007).
Amongst plant foods with health benefits, crops from the family Brassicaceae (also known as Cruciferae) have been the focus of numerous epidemiological and clinical studies (Podsędek 2007) as they are good source of variety of nutrients and health promoting phytochemicals (Liu 2004; Soengas et al. 2011). Brassica vegetables, like knol khol, cabbage, broccoli, cauliflower, kale and Brussels sprouts are widely consumed throughout the world. Folklore medicine have shown that knolkhol/kohlrabi, scientifically known as Brassica oleraceae var gongylodes (BOvG) has health promoting activity and anti-diabetic activity. Previously (Huchaiah et al. 2008) BOvG juice was assessed for hypoglycemic activity and its related biochemical parameters. However, till date phenolic rich extract of BOvG and its components have not been investigated and hence the present investigation assessed anti-diabetic activity of phenolic rich extract of BOvG.
Diabetes is a metabolic disorder of carbohydrate, fat and protein, affecting a large number of populations in the world. The pathogenesis of diabetes involving hyperglycemia, dysregulated metabolism and the ensuing diabetes specific micro as well as macro vascular complications have posed an immense challenge for its overall treatment.
Most modern drug discovery has been based on a ‘one-disease–one-target–one-drug' strategy (Ji et al. 2009). A multifactorial disease like diabetes requires a combination of different types of nutraceuticals that target multiple pathways rather than a selective compound which often target a single pathway. This ‘multi-component therapeutics’ is gaining huge popularity within the scientific community (Ji et al. 2009), and it is imperative that the pharmaceutical industry realize its importance to overcome the challenge of ‘more investment, fewer drugs'.
The polyphenols in Brassica vegetables have immense health improvement potential as these polyphenols have high antioxidant activity (Cartea et al. 2011). Rasal et al. (2005) demonstrated the anti-diabetic and anti-oxidant activities of petroleum extract of knol khol in diabetic rats. The phenolic rich extract in the present study fared better than the petroleum extract, as it achieved euglycemia within one week of treatment. In this study, we have also identified the presence chlorogenic acid (5.9 mg/g), sinapic acid (2.7 mg/g) and rutin (1.6 mg/g) in BOvG. Earlier, chlorogenic acid and its isomers, neo- and cryptochlorogenic acids have been reported in other Brassica species and have been the important predictors for antioxidative capacity in Brassica varieties (Kaulmann et al. 2014).
The most abundant group of polyphenols in Brassica species are the flavonoids and hydroxycinnamic acids (Cartea et al. 2011). Significant levels of chlorogenic acids have previously been reported in leafy Brassica species, like kale, cabbage and Brussels sprouts. Earlier reports have found flavonoid glycosides, hydroxycinnamic acids as well as sinapic acids and their derivatives to be the most predominant phenolics in Brassica sps. (Cartea et al. 2011). In addition to polyphenolics, isothiocynates (hydrolytic products of glucosinolates; a characteristic compound in Brassica), have been identified in early white vienna cultivar of BOvG with 4-methylthiobutyl being the most predominant isothiocynate (Carlson et al. 1987).
In the present investigation, on treating diabetic rats with BOvG extracts, the FBG levels normalized within one week and fared better than the standard drug glibenclamide. This anti-diabetic activity of BOvG extract was possibly attributed to the additive effect of activation of a number of molecular pathways by the various enriched bioactive components. Earlier reports have shown chlorogenic acid stimulates glucose transport in skeletal muscle via the activation of AMPK (Ong et al. 2012) and sinapic acid activates PLC-PKC signals to enhance the glucose utilization GLUT4 in muscle cells (Cherng et al. 2013). Additionally, chlorogenic acid and rutin have shown cholesterol lowering abilities by up-regulating the Gene Expression of PPAR-α (Wan et al. 2013) and by ameliorating oxidative stress genes (Al-Rejaie et al. 2013) respectively.
There are various studies in which different herbal drug combinations have been beneficial for reducing dosage, side effects and the duration of action (Kaur et al. 2013; Rathera et al. 2013). Herbal drugs also have additive effects; thus showing drastic reduction in FBG levels and amelioration of diabetic related complications in BOvG fed rats in this study. In continuation of this study, the combination index of chlorogenic acid, sinapic acid and rutin (the predominant polyphenols found in BOvG) (Rathera et al. 2013; Chou 2006) and the nature of their interactions, needs to be further investigated in a diabetic model.
BOvG has shown in this study and earlier studies (Huchaiah et al. 2008; Rasal et al. 2005) immense potential as a natural alternative to control diabetes. In the short run, BOvG tuber can be an important part of meal planning for diabetic patients in order to manage their post prandial blood glucose level. Moreover, in the longer run, compounds identified in BOvG have the potential to be developed as natural anti-diabetic drugs.
Based on our current findings BOvG significantly reduced FBG to normal levels and alleviated diabetes related complications. We suggest that the phytomolecules in BOvG have the potential to form a multi-component drug to target diabetes and its related complications.Animal Rights:
Ethical clearance of the animal experiment had been approved by the Institutional Animal Ethics Committee of Animal Research (IAEC approval number: UOM/IAEC/09/2012) at DOS in Zoology, University of Mysore, and experiments were carried out as per the guidelines of the committee.
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